TY - JOUR
T1 - Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer
T2 - the letrozole/fulvestrant and avastin (LEA) study
AU - Martín, Miguel
AU - Loibl, Sibylle
AU - von Minckwitz, Gunter
AU - Morales, Serafín
AU - Martinez, Noelia
AU - Guerrero, Angel
AU - Anton, Antonio
AU - Aktas, Bahriye
AU - Schoenegg, Winfried
AU - Muñoz, Montserrat
AU - Garcia-Saenz, José Ángel
AU - Gil, Miguel
AU - Ramos, Manuel
AU - Margeli, Mireia
AU - Carrasco, Eva
AU - Liedtke, Cornelia
AU - Wachsmann, Grischa
AU - Mehta, Keyur
AU - De la Haba-Rodriguez, Juan R
N1 - © 2015 by American Society of Clinical Oncology.
PY - 2015/3/20
Y1 - 2015/3/20
N2 - PURPOSE: To test whether combining bevacizumab, an anti-vascular endothelial growth factor treatment, with endocrine therapy (ET) could potentially delay the emergence of resistance to ET.PATIENTS AND METHODS: A multicenter, randomized, open-label, phase III, binational (Spain and Germany) study added bevacizumab (15 mg/kg every 3 weeks) to ET (ET-B; letrozole or fulvestrant) as first-line therapy in postmenopausal patients with human epidermal growth factor receptor 2 (HER2) -negative and hormone receptor-positive advanced breast cancer. We compared progression-free survival (PFS), overall survival (OS), overall response rate (ORR), response duration (RD), time to treatment failure (TTF), clinical benefit rate (CBR), and safety.RESULTS: From 380 patients recruited (2007 to 2011), 374 were analyzed by intent to-treat (184 patients on ET and 190 patients on ET-B). Median age was 65 years, 270 patients (72%) had Eastern Cooperative Oncology Group performance status of 0, 178 patients (48%) had visceral metastases, and 171 patients (46%) and 195 patients (52%) had received prior chemotherapy or ET, respectively. Median PFS was 14.4 months in the ET arm and 19.3 months in the ET-B arm (hazard ratio, 0.83; 95% CI, 0.65 to 1.06; P = .126). ORR, CBR, and RD with ET versus ET-B were 22% versus 41% (P < .001), 67% versus 77% (P = .041), and 13.3 months versus 17.6 months (P = .434), respectively. TTF and OS were comparable in both arms. Grade 3 to 4 hypertension, aminotransferase elevation, and proteinuria were significantly higher in the ET-B arm. Eight patients (4.2%) receiving ET-B died during study or within 30 days of end of treatment.CONCLUSION: The addition of bevacizumab to ET in first-line treatment failed to produce a statistically significant increase in PFS or OS in women with HER2-negative/hormone receptor-positive advanced breast cancer.
AB - PURPOSE: To test whether combining bevacizumab, an anti-vascular endothelial growth factor treatment, with endocrine therapy (ET) could potentially delay the emergence of resistance to ET.PATIENTS AND METHODS: A multicenter, randomized, open-label, phase III, binational (Spain and Germany) study added bevacizumab (15 mg/kg every 3 weeks) to ET (ET-B; letrozole or fulvestrant) as first-line therapy in postmenopausal patients with human epidermal growth factor receptor 2 (HER2) -negative and hormone receptor-positive advanced breast cancer. We compared progression-free survival (PFS), overall survival (OS), overall response rate (ORR), response duration (RD), time to treatment failure (TTF), clinical benefit rate (CBR), and safety.RESULTS: From 380 patients recruited (2007 to 2011), 374 were analyzed by intent to-treat (184 patients on ET and 190 patients on ET-B). Median age was 65 years, 270 patients (72%) had Eastern Cooperative Oncology Group performance status of 0, 178 patients (48%) had visceral metastases, and 171 patients (46%) and 195 patients (52%) had received prior chemotherapy or ET, respectively. Median PFS was 14.4 months in the ET arm and 19.3 months in the ET-B arm (hazard ratio, 0.83; 95% CI, 0.65 to 1.06; P = .126). ORR, CBR, and RD with ET versus ET-B were 22% versus 41% (P < .001), 67% versus 77% (P = .041), and 13.3 months versus 17.6 months (P = .434), respectively. TTF and OS were comparable in both arms. Grade 3 to 4 hypertension, aminotransferase elevation, and proteinuria were significantly higher in the ET-B arm. Eight patients (4.2%) receiving ET-B died during study or within 30 days of end of treatment.CONCLUSION: The addition of bevacizumab to ET in first-line treatment failed to produce a statistically significant increase in PFS or OS in women with HER2-negative/hormone receptor-positive advanced breast cancer.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Antibodies, Monoclonal, Humanized/administration & dosage
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Bevacizumab
KW - Breast Neoplasms/drug therapy
KW - Disease-Free Survival
KW - Drug Resistance, Neoplasm
KW - Estradiol/adverse effects
KW - Female
KW - Fulvestrant
KW - Germany
KW - Hormones/administration & dosage
KW - Humans
KW - Letrozole
KW - Middle Aged
KW - Nitriles/administration & dosage
KW - Postmenopause
KW - Spain
KW - Treatment Outcome
KW - Triazoles/administration & dosage
KW - Vascular Endothelial Growth Factor A/antagonists & inhibitors
U2 - 10.1200/JCO.2014.57.2388
DO - 10.1200/JCO.2014.57.2388
M3 - Article
C2 - 25691671
SN - 0732-183X
VL - 33
SP - 1045
EP - 1052
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 9
ER -
